Preparation Of Long Circulating Nolatrexed Dihydrochloride Liposomes And The Study On Its Antitumor Activity

As a newly developed non-classic folate antitumor drug, nolatrexed dihydrochloride (NLTX),is a hymidylate synthase(TS) inhibitor. NLTX must be administered via continuous infusion because of short half-life. Clinical applications of NLTX were limited for its most common adverse effects included rash, mucositis, neutropenia and thrombocytopenia. As long circulating liposomal drug-delivery systems were suitable for a number of therapeutic applications involving sustained drug release and selective drug delivery to specific target tissues, nolatrexed dihydrochloride long circulating liposomal (LCL- NLTX) was developed in this study. Toxic effects of LCL- NLTX and the antitumor activity were also observed.Amphipathic polyethylene glycoldistearoyl phosphatidylethanolamine (DSPE-PEG2000), saturated phospholipid HSPC and cholesterol were applied as membrane materials to improve stability of liposome. Ammonium sulfate gradient method and nuclearpore membrane estruding method were combined to improve enveloping rate. To control the quality of LCL-NLTX, NLTX dialysis-ultraviolet light-photometry method was established to accurately detect the enveloping rate and...